The general objective of this research is to determine the three-dimensional geometries of biologically active macromolecules and to correlate these geometries with their function and evolution. The structures of several proteins will be examined by x-ray crystallographic methods. Specific proteins to be studied include subtilisin, chymotrypsinogen, and R. rubrum cytochrome c2, for each of which a model has already been constructed. Also being investigated are the structures of E. coli dihydrofolate reductase, L. caseii dihydrofloate reductase, th 2Fe ferredoxin from Anacystis nidulans, cytochrome f from spirulina maxima and yeast cytochrome c peroxidase.